Aminoalkylated diamino diphenyl sulfones



Patented July 24, 1951 UNITED, STATES PATENT OFFICE v AMINOALKYLATED DIADIINO DII'HENYL SULFON ES Albert L. Rawlins, Grosse Pointe Woods, Mich., assignor to Parke, Davis & Company, Detroit, Mich., a corporation of Michigan No Drawing. Application November 23. 1948,

1 Serial No. 61,741

6 Claims. 260-239-6) NHPQ-SOGNHR where R represents an alkyl radical substituted on a carbon atom thereof by a basic nitrogen group such as an amino, alkylamino, alkenylamino, dialkylamino, dialkenylamino, piperidino, morpholine, pyrrolidino and thiomorpholino groups.

The free base compounds of the above general formula form acid addition salts with both. inorganic and organic acids. Some examples of the salts which may be prepared by the methods cocci, pneumococci and Mycobacterium tubercwlosis. Many of them are efiective as antiseptics upon oral administration. They are of low toxicity and are very stable chemically.

,In accordance with the invention the new products are prepared by reacting p,p'-diaminodiphenyl sulfone with an alkyl halide the alkyl group of which contains a basic nitrogen substituent. This transformation can be diagrammatically illustrated as follows:

NnOsorONm-p RX 7 sulfones can also be prepared by first reacting an alkyl halide substituted in the alkyl group by a phthalimido or similar radical with p,p'- diaminodiphenyl ultone and hydrolyzing the product so obtained to remove the protecting group from amino group. This modification is illustrated in Example 1 below.

The invention is illustrated by the following examples.

Example 1.--p-i4mino-p'-('y-ammopromllamino) diphenyl sulfone grams of 4,4'-diamino diphenyl sulfone, 109 grams of 2-bromopropyl phthalimide, 600 cc. of alcohol and 750 cc. of water are mixed and refluxed for 30 hours. The mixture is cooled and the crystals which form are filtered oil. 40 grams of these crystals are insoluble in alcohol. This alcohol insoluble material is mixed with 200 cc. of alcohol and 11 grams of hydrazine hydrate. The mixture is refluxed for a short time. The entire reaction mixture forms a white solid. Heating on the steam bath is continued for an hour and then most of the alcohol removed by vacuum distillation. The residue is refluxed with 500 cc. of 2% RC1 solution for an Example 2.p-Amino-p'-(- diethylaminopropylamino) diphenyl suljone H HaNO-S OPOIL -CHQCHQ CH1N A mixture consisting of 24 g. of p.p'-diamino diphenyl sulfone, 15.5-g. oi 'y-diethylaminopropyl chloride and suflicient alcohol to dissolve the reactants is heated under reflux for about twelve hours. The alcohol is removed from the reaction mixture by distillation and the residue treated with 500 cc. of water. The solution is made alkaline with 10 N sodium hydroxide solution, the insoluble crude p-amino-p oy-diethyl- 3 4 aminopropylamino) diphenyl sulfone tcolleolted. CH CHCH, and purified by recrystallization from e hano O O b Example 3,-p-Amino-p'(fl-piperidinoethylami- 1 OH, H

no) diphenyl sulfo'ne 5 omen, Nib-GsmONH-omomorrm omomonm NHz-OSOa-ON H-CH:CH:N\ on.

CH; smo

NH so NH- H H H H An alcoholic solution containing 24.6 g. of p, p'- O O 0 i0 CHINE diamino diphenyl sulfone and gof p-piperi- CH.

- dinoethyl bromide is heated under reflux forv twelve hours. The mixture is cooled, treated NEOSOONHHICEN \CECH' with 5% sodium hydroxide, diluted with water and the insoluble product collected. The crude u care 1 p-amino-p-(5-piperidino-ethylamino) diphenyl CH CH sulfone thus obtained is purified by recrystallization from alcohol or alcohol-water mixture. Q' I-ONH-CHaCHwHzN If desired, the hydrobromide or hydrochloride salt of this product can be prepared by adding 20 what I claim is: dry hydmgen brqmlde hydmien chloride to 1. A compound of the class consisting of a free an alcoholic sohmon or t 6 free base and its acid addition salts, said free base Example 4.p- Amino-p(6-morpholinobutylhaving the formula,

amino) diphenyl sulfone \cmcl where Y is an alkylene radical containing two An isopropanol solution containing 24.6 g. of to five carbon atoms and R1 and R: are memp,p'-diamino diphenyl sulfone and 21.8 g. of 6- bers of the class consisting of hydrogen, lower morpholinobutyl bromide is refluxed for twelve alkyl, lower alkenyl radicals, and further memhours. Most of the isopropanol is removed by bers wherein R1 and R2 taken together with S CHzC;

distillation in vacuo, the residue cooled and N= form piperidino, morpholino, Dy rolidino treated with,an excess of 10 N sodium hydroxide. and thiomorpholino groups. The mixture is diluted with water, the insoluble 2. A compound of the formula,

product collected and purified by recrystallization from alcohol. NEH-OS o-z@NH-oH,cH1cH,NH=

Example 5. p-Amino-p' ('y-ethylaminopropylamino) diphenyl sulfone 3. A compound of the formula,

A mixture consisting of 24.6 g. of p,p'-diamino A of the 150mm, diphenyl sulfone and 20 g. of 'y-ethylaminopropyl /CH2CH1 chloride hydrochloride dissolved in isopropanol g is heated under. reflux for twelve hours. Most of o O NH the isopropanol is removed by distillation in vacuo 1 and the cool residue treated with 500 cc. of water. 5. A compound of the formula,

CH2--CH2 H1N-s0, C -NnoH=cmoHT-cm 1v o CH1C2 The resultant mixture is filtered, made strongly 6. A compound of the formula, alkaline with 10 N sodium hydroxide and the insoluble material collected and purified by re- O O crystallization from alcohol. The product so ALBERT RAWLINS obtained is p-amino-p'('y-ethylamino-propylamino) diphenyl sulfone. REFERENCES CITED Some further examples of the products which can be produced by use of the above described g ggg ggf gff are of recqrd m the procedures are: CH UNITED STATES PATENTS NHrO-SO: QNH-oH-omomcmmom Number Name Date 05 2,800,677 Kharasch et al Nov. 3, 1942 

1. A COMPOUND OF THE CLASS CONSISTING OF A FREE BASE AND ITS ACID ADDITION SALTS, SAID FREE BASE HAVING THE FORMULA,
 5. A COMPOUND OF THE FORMULA, 